TEP1_HUMAN
ID TEP1_HUMAN Reviewed; 2627 AA.
AC Q99973; A0AUV9;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Telomerase protein component 1;
DE AltName: Full=Telomerase-associated protein 1;
DE Short=Telomerase protein 1;
DE AltName: Full=p240;
DE AltName: Full=p80 telomerase homolog;
GN Name=TEP1; Synonyms=TLP1, TP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP PRO-116; GLY-553; CYS-1055; GLN-1155 AND PRO-1195.
RX PubMed=9020079; DOI=10.1126/science.275.5302.973;
RA Harrington L., McPhail T., Mar V., Zhou W., Oulton R., Bass M.B.,
RA Arruda I., Robinson M.O.;
RT "A mammalian telomerase-associated protein.";
RL Science 275:973-977(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2288-2627 (ISOFORM 2).
RC TISSUE=Salivary gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP IDENTIFICATION IN THE TELOMERASE RIBONUCLEOPROTEIN COMPLEX.
RX PubMed=9389643; DOI=10.1101/gad.11.23.3109;
RA Harrington L., Zhou W., McPhail T., Oulton R., Yeung D.S., Mar V.,
RA Bass M.B., Robinson M.O.;
RT "Human telomerase contains evolutionarily conserved catalytic and
RT structural subunits.";
RL Genes Dev. 11:3109-3115(1997).
RN [5]
RP IDENTIFICATION IN THE VAULTS RIBONUCLEOPROTEIN PARTICLE, AND RNA-BINDING.
RX PubMed=10551828; DOI=10.1074/jbc.274.46.32712;
RA Kickhoefer V.A., Stephen A.G., Harrington L., Robinson M.O., Rome L.H.;
RT "Vaults and telomerase share a common subunit, TEP1.";
RL J. Biol. Chem. 274:32712-32717(1999).
RN [6]
RP IDENTIFICATION IN THE TELOMERASE RIBONUCLEOPROTEIN COMPLEX.
RX PubMed=11029039; DOI=10.1091/mbc.11.10.3329;
RA Beattie T.L., Zhou W., Robinson M.O., Harrington L.;
RT "Polymerization defects within human telomerase are distinct from
RT telomerase RNA and TEP1 binding.";
RL Mol. Biol. Cell 11:3329-3340(2000).
RN [7]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
RX PubMed=19179534; DOI=10.1126/science.1165357;
RA Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M.,
RA Veenstra T.D., Terns M.P., Artandi S.E.;
RT "A human telomerase holoenzyme protein required for Cajal body localization
RT and telomere synthesis.";
RL Science 323:644-648(2009).
CC -!- FUNCTION: Component of the telomerase ribonucleoprotein complex that is
CC essential for the replication of chromosome termini (PubMed:19179534).
CC Also a component of the ribonucleoprotein vaults particle, a multi-
CC subunit structure involved in nucleo-cytoplasmic transport (By
CC similarity). Responsible for the localizing and stabilizing vault RNA
CC (vRNA) association in the vault ribonucleoprotein particle. Binds to
CC TERC (By similarity). {ECO:0000250|UniProtKB:P97499,
CC ECO:0000269|PubMed:19179534}.
CC -!- SUBUNIT: Associated component of the telomerase holoenzyme complex
CC (PubMed:19179534). Component of the vault ribonucleoprotein particle,
CC at least composed of MVP, PARP4 and one or more vault RNAs (vRNAs) (By
CC similarity). Binds to VAULTRC1, VAULTRC2 and VAULTRC4/hvg4 vRNAs (By
CC similarity). {ECO:0000250|UniProtKB:P97499,
CC ECO:0000269|PubMed:19179534}.
CC -!- INTERACTION:
CC Q99973; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-947859, EBI-372094;
CC Q99973; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-947859, EBI-2514383;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Chromosome, telomere.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99973-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99973-2; Sequence=VSP_010359;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9020079}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an exon inclusion.
CC {ECO:0000305}.
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DR EMBL; U86136; AAC51107.1; -; mRNA.
DR EMBL; BC126107; AAI26108.1; -; mRNA.
DR EMBL; BX640983; CAE45993.1; -; mRNA.
DR CCDS; CCDS9548.1; -. [Q99973-1]
DR RefSeq; NP_009041.2; NM_007110.4. [Q99973-1]
DR RefSeq; XP_005268084.1; XM_005268027.4. [Q99973-1]
DR AlphaFoldDB; Q99973; -.
DR SMR; Q99973; -.
DR BioGRID; 112870; 57.
DR IntAct; Q99973; 7.
DR STRING; 9606.ENSP00000262715; -.
DR BindingDB; Q99973; -.
DR iPTMnet; Q99973; -.
DR PhosphoSitePlus; Q99973; -.
DR SwissPalm; Q99973; -.
DR BioMuta; TEP1; -.
DR DMDM; 215273899; -.
DR EPD; Q99973; -.
DR jPOST; Q99973; -.
DR MassIVE; Q99973; -.
DR MaxQB; Q99973; -.
DR PaxDb; Q99973; -.
DR PeptideAtlas; Q99973; -.
DR PRIDE; Q99973; -.
DR ProteomicsDB; 78559; -. [Q99973-1]
DR ProteomicsDB; 78560; -. [Q99973-2]
DR Antibodypedia; 6875; 109 antibodies from 27 providers.
DR DNASU; 7011; -.
DR Ensembl; ENST00000262715.10; ENSP00000262715.5; ENSG00000129566.13. [Q99973-1]
DR GeneID; 7011; -.
DR KEGG; hsa:7011; -.
DR MANE-Select; ENST00000262715.10; ENSP00000262715.5; NM_007110.5; NP_009041.2.
DR UCSC; uc001vxe.4; human. [Q99973-1]
DR CTD; 7011; -.
DR DisGeNET; 7011; -.
DR GeneCards; TEP1; -.
DR HGNC; HGNC:11726; TEP1.
DR HPA; ENSG00000129566; Low tissue specificity.
DR MIM; 601686; gene.
DR neXtProt; NX_Q99973; -.
DR OpenTargets; ENSG00000129566; -.
DR PharmGKB; PA36443; -.
DR VEuPathDB; HostDB:ENSG00000129566; -.
DR eggNOG; KOG3602; Eukaryota.
DR eggNOG; KOG4155; Eukaryota.
DR GeneTree; ENSGT00940000161338; -.
DR InParanoid; Q99973; -.
DR OMA; WINKPQT; -.
DR OrthoDB; 29963at2759; -.
DR PhylomeDB; Q99973; -.
DR TreeFam; TF328424; -.
DR PathwayCommons; Q99973; -.
DR SignaLink; Q99973; -.
DR BioGRID-ORCS; 7011; 4 hits in 1081 CRISPR screens.
DR ChiTaRS; TEP1; human.
DR GeneWiki; TEP1; -.
DR GenomeRNAi; 7011; -.
DR Pharos; Q99973; Tbio.
DR PRO; PR:Q99973; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q99973; protein.
DR Bgee; ENSG00000129566; Expressed in monocyte and 159 other tissues.
DR ExpressionAtlas; Q99973; baseline and differential.
DR Genevisible; Q99973; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016363; C:nuclear matrix; IDA:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; TAS:UniProtKB.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0003720; F:telomerase activity; IEA:Ensembl.
DR GO; GO:0070034; F:telomerase RNA binding; ISS:BHF-UCL.
DR GO; GO:0000722; P:telomere maintenance via recombination; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; -; 6.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR025139; DUF4062.
DR InterPro; IPR045804; DUF5920.
DR InterPro; IPR007111; NACHT_NTPase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR008850; TEP1_N.
DR InterPro; IPR008858; TROVE_dom.
DR InterPro; IPR037214; TROVE_dom_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF13271; DUF4062; 1.
DR Pfam; PF19334; DUF5920; 1.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF05386; TEP1_N; 4.
DR Pfam; PF05731; TROVE; 1.
DR Pfam; PF00400; WD40; 5.
DR SMART; SM00320; WD40; 18.
DR SUPFAM; SSF140864; SSF140864; 1.
DR SUPFAM; SSF50978; SSF50978; 3.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50837; NACHT; 1.
DR PROSITE; PS51226; TEP1_N; 4.
DR PROSITE; PS50988; TROVE; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 7.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromosome; Nucleotide-binding; Nucleus;
KW Reference proteome; Repeat; Ribonucleoprotein; RNA-binding; Telomere;
KW WD repeat.
FT CHAIN 1..2627
FT /note="Telomerase protein component 1"
FT /id="PRO_0000050982"
FT REPEAT 1..30
FT /note="TEP1 N-terminal 1"
FT REPEAT 31..60
FT /note="TEP1 N-terminal 2"
FT REPEAT 61..90
FT /note="TEP1 N-terminal 3"
FT REPEAT 91..120
FT /note="TEP1 N-terminal 4"
FT DOMAIN 223..676
FT /note="TROVE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00343"
FT DOMAIN 1162..1490
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 1411..1448
FT /note="WD 1"
FT REPEAT 1674..1713
FT /note="WD 2"
FT REPEAT 1716..1754
FT /note="WD 3"
FT REPEAT 1757..1796
FT /note="WD 4"
FT REPEAT 1798..1837
FT /note="WD 5"
FT REPEAT 1840..1879
FT /note="WD 6"
FT REPEAT 1882..1921
FT /note="WD 7"
FT REPEAT 1925..1964
FT /note="WD 8"
FT REPEAT 1967..2005
FT /note="WD 9"
FT REPEAT 2008..2047
FT /note="WD 10"
FT REPEAT 2059..2098
FT /note="WD 11"
FT REPEAT 2105..2143
FT /note="WD 12"
FT REPEAT 2146..2183
FT /note="WD 13"
FT REPEAT 2185..2233
FT /note="WD 14"
FT REPEAT 2236..2275
FT /note="WD 15"
FT REPEAT 2278..2317
FT /note="WD 16"
FT REPEAT 2319..2355
FT /note="WD 17"
FT REPEAT 2368..2417
FT /note="WD 18"
FT REPEAT 2459..2500
FT /note="WD 19"
FT REPEAT 2553..2590
FT /note="WD 20"
FT REPEAT 2592..2626
FT /note="WD 21"
FT REGION 193..214
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2506..2551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2506..2538
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1168..1175
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VAR_SEQ 2475..2506
FT /note="ESSFLCASSDGILWNLAKCSPEGEWTTGNMWQ -> ALMGSYGTWPNAAQKE
FT NGPQVTCGR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_010359"
FT VARIANT 116
FT /note="S -> P (in dbSNP:rs1760897)"
FT /evidence="ECO:0000269|PubMed:9020079"
FT /id="VAR_018490"
FT VARIANT 137
FT /note="T -> M (in dbSNP:rs10083536)"
FT /id="VAR_047631"
FT VARIANT 307
FT /note="N -> K (in dbSNP:rs1760898)"
FT /id="VAR_018491"
FT VARIANT 368
FT /note="K -> R (in dbSNP:rs2228035)"
FT /id="VAR_047632"
FT VARIANT 434
FT /note="K -> N (in dbSNP:rs17111188)"
FT /id="VAR_047633"
FT VARIANT 510
FT /note="S -> L (in dbSNP:rs4982051)"
FT /id="VAR_047634"
FT VARIANT 553
FT /note="A -> G (in dbSNP:rs76466486)"
FT /evidence="ECO:0000269|PubMed:9020079"
FT /id="VAR_047635"
FT VARIANT 933
FT /note="R -> H (in dbSNP:rs34179031)"
FT /id="VAR_047636"
FT VARIANT 1055
FT /note="R -> C (in dbSNP:rs1760903)"
FT /evidence="ECO:0000269|PubMed:9020079"
FT /id="VAR_018492"
FT VARIANT 1155
FT /note="R -> Q (in dbSNP:rs2228041)"
FT /evidence="ECO:0000269|PubMed:9020079"
FT /id="VAR_047637"
FT VARIANT 1195
FT /note="S -> P (in dbSNP:rs1760904)"
FT /evidence="ECO:0000269|PubMed:9020079"
FT /id="VAR_018493"
FT VARIANT 1351
FT /note="R -> Q (in dbSNP:rs12886088)"
FT /id="VAR_047638"
FT VARIANT 1408
FT /note="G -> R (in dbSNP:rs2229100)"
FT /id="VAR_047639"
FT VARIANT 1447
FT /note="S -> T (in dbSNP:rs1713457)"
FT /id="VAR_018494"
FT VARIANT 1468
FT /note="C -> Y (in dbSNP:rs1713456)"
FT /id="VAR_018495"
FT VARIANT 1661
FT /note="R -> Q (in dbSNP:rs34401320)"
FT /id="VAR_047640"
FT VARIANT 1772
FT /note="R -> Q (in dbSNP:rs8022805)"
FT /id="VAR_047641"
FT VARIANT 2214
FT /note="V -> I (in dbSNP:rs1713449)"
FT /id="VAR_018496"
FT VARIANT 2310
FT /note="A -> S (in dbSNP:rs35929175)"
FT /id="VAR_047642"
FT VARIANT 2486
FT /note="I -> M (in dbSNP:rs938886)"
FT /id="VAR_018497"
FT VARIANT 2562
FT /note="H -> R (in dbSNP:rs2104978)"
FT /id="VAR_018498"
SQ SEQUENCE 2627 AA; 290490 MW; 32628238704A8860 CRC64;
MEKLHGHVSA HPDILSLENR CLAMLPDLQP LEKLHQHVST HSDILSLKNQ CLATLPDLKT
MEKPHGYVSA HPDILSLENQ CLATLSDLKT MEKPHGHVSA HPDILSLENR CLATLSSLKS
TVSASPLFQS LQISHMTQAD LYRVNNSNCL LSEPPSWRAQ HFSKGLDLST CPIALKSISA
TETAQEATLG RWFDSEEKKG AETQMPSYSL SLGEEEEVED LAVKLTSGDS ESHPEPTDHV
LQEKKMALLS LLCSTLVSEV NMNNTSDPTL AAIFEICREL ALLEPEFILK ASLYARQQLN
VRNVANNILA IAAFLPACRP HLRRYFCAIV QLPSDWIQVA ELYQSLAEGD KNKLVPLPAC
LRTAMTDKFA QFDEYQLAKY NPRKHRAKRH PRRPPRSPGM EPPFSHRCFP RYIGFLREEQ
RKFEKAGDTV SEKKNPPRFT LKKLVQRLHI HKPAQHVQAL LGYRYPSNLQ LFSRSRLPGP
WDSSRAGKRM KLSRPETWER ELSLRGNKAS VWEELIENGK LPFMAMLRNL CNLLRVGISS
RHHELILQRL QHAKSVIHSR QFPFRFLNAH DAIDALEAQL RNQALPFPSN ITLMRRILTR
NEKNRPRRRF LCHLSRQQLR MAMRIPVLYE QLKREKLRVH KARQWKYDGE MLNRYRQALE
TAVNLSVKHS LPLLPGRTVL VYLTDANADR LCPKSNPQGP PLNYALLLIG MMITRAEQVD
VVLCGGDTLK TAVLKAEEGI LKTAIKLQAQ VQEFDENDGW SLNTFGKYLL SLAGQRVPVD
RVILLGQSMD DGMINVAKQL YWQRVNSKCL FVGILLRRVQ YLSTDLNPND VTLSGCTDAI
LKFIAEHGAS HLLEHVGQMD KIFKIPPPPG KTGVQSLRPL EEDTPSPLAP VSQQGWRSIR
LFISSTFRDM HGERDLLLRS VLPALQARAA PHRISLHGID LRWGVTEEET RRNRQLEVCL
GEVENAQLFV GILGSRYGYI PPSYNLPDHP HFHWAQQYPS GRSVTEMEVM QFLNRNQRLQ
PSAQALIYFR DSSFLSSVPD AWKSDFVSES EEAARRISEL KSYLSRQKGI TCRRYPCEWG
GVAAGRPYVG GLEEFGQLVL QDVWNMIQKL YLQPGALLEQ PVSIPDDDLV QATFQQLQKP
PSPARPRLLQ DTVQRLMLPH GRLSLVTGQS GQGKTAFLAS LVSALQAPDG AKVASLVFFH
FSGARPDQGL ALTLLRRLCT YLRGQLKEPG ALPSTYRSLV WELQQRLLPK SAESLHPGQT
QVLIIDGADR LVDQNGQLIS DWIPKKLPRC VHLVLSVSSD AGLGETLEQS QGAHVLALGP
LEASARARLV REELALYGKR LEESPFNNQM RLLLVKRESG RPLYLRLVTD HLRLFTLYEQ
VSERLRTLPA TVPLLLQHIL STLEKEHGPD VLPQALTALE VTRSGLTVDQ LHGVLSVWRT
LPKGTKSWEE AVAAGNSGDP YPMGPFACLV QSLRSLLGEG PLERPGARLC LPDGPLRTAA
KRCYGKRPGL EDTAHILIAA QLWKTCDADA SGTFRSCPPE ALGDLPYHLL QSGNRGLLSK
FLTNLHVVAA HLELGLVSRL LEAHALYASS VPKEEQKLPE ADVAVFRTFL RQQASILSQY
PRLLPQQAAN QPLDSPLCHQ ASLLSRRWHL QHTLRWLNKP RTMKNQQSSS LSLAVSSSPT
AVAFSTNGQR AAVGTANGTV YLLDLRTWQE EKSVVSGCDG ISACLFLSDD TLFLTAFDGL
LELWDLQHGC RVLQTKAHQY QITGCCLSPD CRLLATVCLG GCLKLWDTVR GQLAFQHTYP
KSLNCVAFHP EGQVIATGSW AGSISFFQVD GLKVTKDLGA PGASIRTLAF NVPGGVVAVG
RLDSMVELWA WREGARLAAF PAHHGFVAAA LFLHAGCQLL TAGEDGKVQV WSGSLGRPRG
HLGSLSLSPA LSVALSPDGD RVAVGYRADG IRIYKISSGS QGAQGQALDV AVSALAWLSP
KVLVSGAEDG SLQGWALKEC SLQSLWLLSR FQKPVLGLAT SQELLASASE DFTVQLWPRQ
LLTRPHKAED FPCGTELRGH EGPVSCCSFS TDGGSLATGG RDRSLLCWDV RTPKTPVLIH
SFPACHRDWV TGCAWTKDNL LISCSSDGSV GLWDPESGQR LGQFLGHQSA VSAVAAVEEH
VVSVSRDGTL KVWDHQGVEL TSIPAHSGPI SHCAAAMEPR AAGQPGSELL VVTVGLDGAT
RLWHPLLVCQ THTLLGHSGP VRAAAVSETS GLMLTASEDG SVRLWQVPKE ADDTCIPRSS
AAVTAVAWAP DGSMAVSGNQ AGELILWQEA KAVATAQAPG HIGALIWSSA HTFFVLSADE
KISEWQVKLR KGSAPGNLSL HLNRILQEDL GVLTSLDWAP DGHFLILAKA DLKLLCMKPG
DAPSEIWSSY TENPMILSTH KEYGIFVLQP KDPGVLSFLR QKESGEFEER LNFDINLENP
SRTLISITQA KPESESSFLC ASSDGILWNL AKCSPEGEWT TGNMWQKKAN TPETQTPGTD
PSTCRESDAS MDSDASMDSE PTPHLKTRQR RKIHSGSVTA LHVLPELLVT ASKDRDVKLW
ERPSMQLLGL FRCEGSVSCL EPWLGANSTL QLAVGDVQGN VYFLNWE
